Matthew Junker, Ph.D.
Associate Professor of Chemistry
Faculty Advisor, Biochemistry Program
Department of Physical Sciences • Program in Chemistry
314 Boehm Science Center FAX: (610) 683-1352
Phone: (610) 683-4199 Email: email@example.com
Courses Taught: Biochemistry and Chemistry
CHM 310, CHM 311 Biochemistry I with laboratory lecture syllabus lab syllabus
CHM 312, CHM 313 Biochemistry II with laboratory lecture syllabus lab syllabus
CHM 215 Organic Chemistry I laboratory
CHM 217 Organic Chemistry II laboratory
CHM 318 Advanced Biochemistry
CHM 370, 371 Research in Chemistry
CHM 380 Senior Seminar in Chemistry
Course materials available online at Desire2Learn
Research: Protein Structure and Function in
Apoptosis, Gene Expression, and Bacteria Pathogenesis
Current student researchers: Will Blakely, Scott Dougherty, Demetrios Kostomiris, Robert Nwokonko
Prior KU student researchers: Haley Andersen, James Bowalick, Lindy Carpenter, Ethan Daniels, Marcela Ferreira, Larry Fredericks, Kevin Frey, Stephanie Hoppes, Heather Jones, Patrick McCaffrey, Stephen Pearson, John Ponis, Josh Sabatine, Drew Tietz, Robert Wagner, Kyle Webb, Courtney Young
Many cellular processes are carried out by proteins, tiny machines that catalyze chemical reactions, transport molecules within and between cells, provide cell architecture, and regulate gene expression and cell growth. The ability of proteins to carry out specific processes depends on their structure and energetics: active site geometries, complementation of recognition surfaces, conformational changes, affinities, stability of folds. In this laboratory, we investigate the molecular mechanism of proteins that function in programmed cell death, gene expression, and bacterial pathogenesis.
All projects generally follow a common set of steps:
1. Use recombinant DNA methods (cloning) to insert into bacteria the genes for proteins of interest.
2. Grow bacteria to make the proteins of interest.
3. Lyse (break open) the bacteria and purify the proteins of interest.
4. Carry out complementary functional (biochemical assays) and structural studies of the purified proteins.
Example: Studies of apoptosis
Apoptosis (programmed cell death) is a process in all animals that eliminates unneeded or unhealthy cells, such as aged cells that need to be regenerated or cells that are at risk for causing cancer. Dysfunction in apoptosis can lead to cancer or neurodegenerative diseases. At a biochemical level, apoptosis requires the activation of caspase enzymes. Caspases are normally held in check by the Inhibitor of Apoptosis (IAP) proteins. Certain apoptosis stimulators bind to IAPs to de-inhibit (activate) caspases.
Studies in living cells had shown that alteration of a highly conserved Arg amino acid in IAPs caused dysfunction in apoptosis. Using purified proteins and a protein binding assay, this laboratory showed that the dysfunction resulted from a loss in the ability of the IAP to bind to apoptosis stimulators (above, right).
Structure analysis (including CD) then determined that the impaired binding was caused by an altered conformation of the IAP protein. Analysis of published IAP structures revealed that the conserved Arg makes several critical interactions (bridging hydrogen bonds, cation-p, helix-capping) that stabilize the IAP tertiary structure. No other amino acid can make this same set of interactions. Since the Arg resides on a face of the IAP opposite to where stimulators bind, it may be important for allosterically coupling stimulator binding to other IAP functions.
Other studies are investigating the mechanism for how IAPs regulate the enzymatic activity of caspases. One assay measures caspase activity by the increased fluorescence when the capase cleaves a synthetic substrate mimic.
The information gained from these studies is providing detailed insight into how these proteins regulate apoptosis in living cells. It should also aid in developing therapies to treat diseases where apoptosis dysfunction occurs, such as cancer and neurodegeneration.
Kutztown University Research Committee 1/13-7/14
"Substrate recognition and ligation mechanisms of yeast cytochrome c $7,662
Co-PI's: Dr. Carsten Sanders and Dr. Matt Junker
Kutztown University Research Committee 1/10-6/11
"Probing the role of CCHL (cytochrome c heme lyase) in apoptosis" $4,360
Co-PI's: Dr. Carsten Sanders and Dr. Matt Junker
Kutztown University Research Committee 1/07-6/08
"Using DNA computing to solve a mathematical problem" $3,550
Co-PI's: Dr. Fran Vasko and Dr. Matt Junker
PA State System of Higher Education 7/06-7/07
"A new method to control protein-protein interactions for studying apoptosis $5,800
(programmed cell death)"
Kutztown University Research Committee 6/06-6/07
"Testing a Potential New Mechanism for How Cells Undergo Programmed $2,500
Cell Death (Apoptosis)"
Kutztown Undergraduate Research Committee (awarded to student) 2/06-6/06
"Identifying the binding region for the Cry1A toxin on the BT-R1 receptor protein" $500
Student principal investigator: Lindy Carpenter
Commonwealth of PA Dept. of Labor & Industry 7/06-7/07
"Microplate reader technology for preparing students at Kutztown University $47,600
for jobs in the bio-medical industry cluster"
American Cancer Society Institutional Research Allocation Grant 1/04-12/04
"Characterization of Apoptosis Proteins as Therapeutic Targets in Cancer" $20,000
1. Junker, M. (2010) "A hands-on classroom simulation to demonstrate concepts in enzyme kinetics."
J. Chem. Ed., 87: 294-295.
2. Ibrahim, M.A., Griko, N., Junker, M., and Bulla, L.A. (2010) "Bacillus thuringiensis: a genomics
and proteomics perspective." Bioengineered Bugs, 1: 31-50.
3. Griko, N.B., Rose-Young, L., Zhang, X., Candas, M., L. Carpenter, L., Ibrahim, M.A., Junker, M.,
and Bulla, L.A. (2007) "Univalent binding of the Cry1Ab toxin of Bacillus thuringiensis to a
conserved motif in the cadherin receptor BT-R1." Biochemistry, 46: 10001-10007.
4. Kou, W., Ortiz-Acevedo, A., Kolla, H.S., Haines, D., Junker, M., and Dieckmann, G.R.(2005)
"Modulation of zinc- and cobalt-binding affinities through changes in the stability of the
zinc ribbon protein L36." J. Biol. Inorg. Chem.,10: 167-180.
5. Wang, L.L., Denman, I., and Junker, M. (2004) "Control of HAP1 DNA site recognition
through the interplay of multiple distinct intermolecular interactions." Biochemistry,
6. Griko, N., Candas, M., Zhang, X., Junker, M., and Bulla, L.A. (2004) "Selective
antagonism of the cadherin BT-R1 interferes with calcium-induced adhesion of epithelial
membrane vesicles." Biochemistry, 43: 1393-1400.
7. Harrod, C.A., Yang, X., Junker, M., and Reitzer, L. (2004) "Evidence for a second
interaction between the regulatory amino-terminal and central output domains of the response
regulator NtrC (Nitrogen Regulator I) in Escherichia coli." J. Biol. Chem. 279: 2350-2359.
8. Luque, L.E., Grape, K.G., and Junker, M. (2002) "A highly conserved arginine is critical for
the functional folding of inhibitor of apoptosis (IAP) protein BIR domains."
Biochemistry 41: 13663-13671.
9. Upadhyaya, A., Khan, M., Mou, T.-C., Junker, M., Gray, D.M., and DeJong, J. (2002)
"The germ-specific transcription factor ALF: structural properties and stabilization of the
TBP-DNA complex." J. Biol. Chem. 277: 34208-34216.
10. Junker, M., Rodgers, K.K., and Coleman, J.E. (1998) "Zinc as a structural and folding
element of proteins which interact with DNA." Inorg. Chim. Acta 275-276: 481-492.
Kutztown University of Pennsylvania
A member of the State System of Higher Education
last modified2/8/13 by M. Junker